The tumors that normal liver, catilage, or muscle cells yield have very different properties. There is no "generalized" malignant cell, only different kinds of malignant cells derived from different types of normal cells. Malignant cells, including the most "undifferentiated," retain to varying degrees genetic properties characterizing their cells of origin. Tumor cells do not return to a more "primitive" or "embryonic" state; rather they represent a further stage in the evolution of a particular lineage. This proposal describes experiments stressing the obligatory requirement for DNA synthesis and ensuing "quantal" cell cycles in moving normal differentiating cells from one compartment in a cell lineage to the next. Normal differentiation, it is proposed, depends upon a small sequence of quantal cell cycles alternating with variable numbers of proliferative cell cycles. Quantal cell cycles lead to daughter cells with synthetic properties strikingly different from those displayed by the mother cell; proliferative cell cycles lead to daughters with the same metabolic repertoire as that of the mother cell into a malignant daughter cell, and that subsequent increase in numbers of that malignant cell involves proliferative cell cycles. Experiments outlined, many using BuDR, 3H-glucosamine, 3H-proline, and other appropriately labelled precursors to proteins and nucleic acids to follow aspects of normal differentiation of myogenic, chondrogenic, and erythrogenic cells, particularly as related to (1) DNA synthesis and to (2) experiments using the same methodologies and theoretical concepts to follow normal myogenic and chondrogenic cells as they change into viral transformed myogenic and chondrogenic cells in vitro, as well as changing into rhabdomyosarcoma and chondrosarcoma in vivo. BIBLIOGRAPHIC REFERENCES: Dienstman, S.R. and Holtzer, H., 1975. Myogenesis: A cell lineage interpretation, In: Results and Problems in Cell Differentiation, Vol. 7, J. Reinert and H. Holtzer , eds., Springer-Verlag. Holtzer, H. and Holtzer, S., 1976. Lineages, quantal cell cycles and cell diversification. In: Progress in Differentiation Research, N. Muller-Berat, et al, eds., North-Holland Publishing Company.